1. TXNIP Maintains the Hematopoietic Cell Pool by Switching the Function of p53 under Oxidative Stress.
- Author
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Jung, Haiyoung, Kim, Mi Jeong, Kim, Dong Oh, Kim, Won Sam, Yoon, Sung-Jin, Park, Young-Jun, Yoon, Suk Ran, Kim, Tae-Don, Suh, Hyun-Woo, Yun, Sohyun, Min, Jeong-Ki, Lee, Hee Gu, Lee, Young Ho, Na, Hee-Jun, Lee, Dong Chul, Kim, Hyoung-Chin, and Choi, Inpyo
- Abstract
Summary: Reactive oxygen species (ROS) are critical determinants of the fate of hematopoietic stem cells (HSCs) and hematopoiesis. Thioredoxin-interacting protein (TXNIP), which is induced by oxidative stress, is a known regulator of intracellular ROS. Txnip
−/− old mice exhibited elevated ROS levels in hematopoietic cells and showed a reduction in hematopoietic cell population. Loss of TXNIP led to a dramatic reduction of mouse survival under oxidative stress. TXNIP directly regulated p53 protein by interfering with p53- mouse double minute 2 (MDM2) interactions and increasing p53 transcriptional activity. Txnip−/− mice showed downregulation of the antioxidant genes induced by p53. Introduction of TXNIP or p53 into Txnip−/− bone marrow cells rescued the HSC frequency and greatly increased survival in mice following oxidative stress. Overall, these data indicate that TXNIP is a regulator of p53 and plays a pivotal role in the maintenance of the hematopoietic cells by regulating intracellular ROS during oxidative stress. [Copyright &y& Elsevier]- Published
- 2013
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